A Photo-Triggered Traceless Staudinger–Bertozzi Ligation Reaction

Article abstract of DOI:10.1002/chem.201601807

The use of light to control the course of a chemical/biochemical reaction is an attractive idea because of its ease of administration with high precision and fine spatial resolution. Staudinger ligation is one of the commonly adopted conjugation processes that involve a spontaneous reaction between azides and arylphosphines to form iminophosphoranes, which further hydrolyze to give stable amides. We designed an anthracenylmethyl diphenylphosphinothioester (1) that showed promising Staudinger ligation reactivity upon photo-excitation. Broadband photolysis at 360–400 nm in aqueous organic solvents induced heterolytic cleavage of its anthracenylmethyl–phosphorus bond, releasing a diphenylphosphinothioester (2) as an efficient traceless Staudinger–Bertozzi ligation reagent. The quantum yield of such a photo-induced heterolytic bond-cleavage at the optimal wavelength of photolysis (376 nm) at room temperature is ≥0.07. This work demonstrated the feasibility of photocaging arylphosphines to realize the photo-triggering of the Staudinger ligation reaction.

Full text of DOI:10.1002/chem.201601807

A Journal of
Accepted Article
Title: A Photo-triggered Traceless Staudinger-Bertozzi Ligation Reaction
Authors: Peng Hu; Tianshi Feng; Chi-Chung Yeung; Chi-Kin Koo; Kai-Chung Lau;
Michael Hon-Wah Lam
This manuscript has been accepted after peer review and the authors have elected
to post their Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by using the Digital
Object Identifier (DOI) given below. The VoR will be published online in Early View as
soon as possible and may be different to this Accepted Article as a result of editing.
Readers should obtain the VoR from the journal website shown below when it is pu-
blished to ensure accuracy of information. The authors are responsible for the content
of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201601807
Link to VoR: http://dx.doi.org/10.1002/chem.201601807
Supported by

Chemistry - A European Journal
10.1002/chem.201601807
COMMUNICATION
A Photo-triggered Traceless Staudinger-Bertozzi Ligation
Reaction
[a]
[a,b,c]
[a]
[a]
[a]
Peng Hu, Tianshi Feng,
Chi-Chung Yeung, Chi-Kin Koo, Kai-Chung Lau, Michael H. W.
[
a]
Lam*
8
Abstract: The use of light to control the course of
a
These include photo-induced thiol-ene/thiol-yne coupling , and
9
chemical/biochemical reaction is an attractive idea because of its
ease of administration with high precision and fine spatial resolution.
Staudinger ligation is one of the commonly adopted conjugation
processes that involve a spontaneous reaction between azides and
arylphosphines to form iminophosphoranes, which further hydrolyze
to stable amides. We designed an anthracenylmethyl
diphenylphosphinothioester (1) that showed promising Staudinger
ligation reactivity upon photo-excitation. Broadband photolysis at 360
photo-induced nitrile imine tetrazole-ene cycloaddition , photo-
1
0
11
enol reaction , copper-free acetylene-azide cycloaddition , and
1
2
photo-induced Diels-Alder [4+2] cycloaddition .
–
400 nm in aqueous organic solvents induced heterolytic cleavage
its anthracenylmethyl-phosphorus bond, releasing
of
a
diphenylphosphinothioester (2) as an efficient traceless Staudinger-
Bertozzi ligation reagent. The quantum yield of such a photo-induced
heterolytic bond-cleavage at the optimal wavelength of photolysis
(376 nm) at room temperature is  0.07. This work demonstrated the
feasibility of photocaging arylphosphines to realize the photo-
triggering of Staudinger ligation reaction.
The spontaneous and clean reaction between azides and
arylphosphines to form iminophosphoranes under mild
conditions was first reported by Staudinger and Meyer in 1919.
Scheme 1. Photo-triggered traceless Staudinger-Bertozzi ligation mediated
by the 9-anthracenylmethyl phosphonium salt 1.
1
In aqueous media, the resulting iminophosphoranes readily
hydrolyze to the corresponding primary amines and phosphine
2
oxides. Potentials of Staudinger reaction in bioconjugation was
Photolysis of arylphosphonium cations has been studied
for over three decades. It has been established that photolysis
of arenylmethyl- and benzhydryl triarylphosphonium cations
would lead to the cleavage of the methylene-phosphorus bond,
recognized by Bertozzi and co-workers in 2000. A series of
arylphosphines were modified with biochemical probes and
electrophilic traps to capture the iminophosphoranes generated
13
3
from azide-modified biomolecules or cellular features.
either via
a
homolytic cleavage pathway to generate
Staudinger-Bertozzi ligation has been recognized as one of
arenylmethyl / benzhydryl radicals and triarylphosphine radical
4
candidate reactions of “Click Chemistry”.
cations, or
arenylmethyl
a
/
heterolytic cleavage pathway to produce
benzhydryl cations and triarylphosphines
Many photo-induced processes, such as photo-lithography,
are now standard techniques in materials and microelectronic
14
(
Scheme S1 of Supporting Information). Peranovich et al.
reported
the
photolysis
of
9-anthracenylmethyl
5
fabrication. They enable precise spatial and temporal control of
triphenylphosphonium chloride in degassed isopropanol
molecular conjugation events. Photo-inducible bioorthogonal
reactions for bio-labeling and metabolic studies are also
becoming increasingly popular in biomedical and chemical
13c
producing triphenylphosphine at 25 % yield. Yet, most of the
subsequent studies focused on the photolytic generation of
carbocations, with little attention paid to the resulting
triarylphosphines. In this context, we designed and synthesized
6
biology research. Numerous “photo-click” reactions have been
developed in the recent decade, and many of them have already
a
9-anthracenylmethyl diphenylphosphonium chloride (1)
7
found applications in materials science and bioimaging fields.
containing an electrophilic thioester moiety and revealed its
potential as a photo-triggered traceless Staudinger-Bertozzi
reagent (Scheme 1).
[
a]
P. Hu, T. Feng, C. C. Yeung, Dr. C.-K. Koo, Dr. K. C. Lau, Dr. M. H.-
W. Lam
Department of Chemistry and Biology
City University of Hong Kong
Fig. 1 shows the molecular structure of 1 (chloride salt)
revealed by X-ray crystallography. An outline of its synthetic
route, which involves the convenient nucleophilic attack of 9-
83 Tat Chee Avenue, Hong Kong SAR, China
E-mail (MHW Lam): bhmhwlam@cityu.edu.hk
T. Feng
Advanced Laboratory for Environmental Research & Technology,
USTC-CityU, Suzhou, China.
(
chloromethyl)anthracene by the phosphinothioester (2)
[
[
b]
c]
15
precursor originally reported by Raines and co-workers , is
given in Scheme 2. 1 is soluble in water, polar organic solvents
and aqueous organic solvents, including aqueous THF. Fig. 2
shows the NMR and the UV-vis absorption properties of 1 in
T. Feng
CAS Key Laboratory of Soft Matter Chemistry, Department of
Polymer Science and Engineering, University of Science and
Technology of China, Hefei, Anhui 230026, China.
Co-corresponding authors
3
1
CDCl
3 3
and aqueous THF. P NMR of 1 in CDCl shows only
*
16
one singlet at 22.5 ppm which is typical of a phosphonium-P.
Supporting information for this article is given via a link at the end of
the document.

Chemistry - A European Journal
10.1002/chem.201601807
COMMUNICATION
1
7
UV-vis absorption of 1 in 300 – 450 nm is dominated by the
formation of 2 by ferrioxalate actinometry was hampered by
the lack of absolute Fe(II) of the ferrioxalate system at 376 nm.
Nevertheless, measurement at 366 nm revealed the quantum
intramolecular (anthryl)
*(diarylphosphine) transitions. Broadband photolysis of 1 in
degassed aqueous organic media at 360 – 400 nm was
 *(anthryl) and (anthryl) 

2
yield of the photo-generation of 2 in 3:1 THF/H O to be 0.07 at
room temperature via GC-MS quantification. Thus, the quantum
efficiency of the photolysis at optimal wavelength should be 
7 %. Under broadband irradiation of 1 in 3:1 THF/H
400 nm, the ultimate yield of 2 was found to be ca. 58%. This
result suggests that heterolytic cleavage of the
anthrylmethylene-phosphorus bond is the predominant pathway
of the photolysis of 1. It is probable that the anthracenylmethyl
moiety in 1 facilitates such a heterolytic photo-induced cleavage
of the anthracenylmethyl-phosphorus bond via the stabilization
of the resultant carbocation by its extensively conjugated
aromatic system. The electron-rich anthryl moiety may also
reduce the rate of geminate recombination of the carbocation
and the phosphine within the geminate solvent cage upon
1
31
monitored by H- & P NMR spectroscopy. Fig. 3 shows the
1
31
shift of H- & P NMR signals in a typical photolysis experiment
in 3:1 d -THF/D O at room temperature. After 10 min. of
8
2
2
O at 360 –
broadband irradiation by a 500W Hg lamp, 1 was converted
back to its precursor phosphinothioester 2. Evidence of
photolytic cleavage of the anthrylmethylene-phosphorus bond
was also obtained from the photolysis of 1 in degassed aqueous
THF, and absolute MeOH where 9-anthracenemethanol and 9-
anthryl methyl ether, respectively, were isolated and
1
characterized by H NMR (Fig. S1 of Supporting Information).
3
1
Subsequent P NMR experiments have established that clean
photolytic conversion of 1 to 2 was observed in degassed d
DMF, CD OD, d -DMF/D O, CD CN/D O and d -THF/D O, while
7
-
3
7
2
3
2
8
2
1
4b
the phosphine oxide of 2 and another unidentified, phosphorus-
containing species were the major products in other solvent
systems (Fig. S2 – S9 of Supporting Information). The effect of
solvents on the photolysis of 1 is not yet well understood at the
moment and warrants further investigation.
photolysis.
1
31
3
Figure 2. Spectroscopic properties of 1: H & P NMR spectra (CDCl ) and
-
5
Scheme 2. Synthesis of the 9-anthracenylmethyl phosphonium salt 1.
UV-vis absorption spectrum (5  10 M) in 3:1 THF/H O.
2
The photo-liberated phosphinothioester
2 has been
reported by Raines and co-workers to be an efficacious
1
8
traceless Staudinger-Bertozzi reagent. Upon reaction with
azides, the thioester moiety acts as an intramolecular cleavable
electrophilic trap on the iminophosphorane intermediates and
converts them into stable amides. Here, we studied reactions of
1
with three aliphatic azides 8, 9 and 10 in degassed aqueous
THF at room temperature in the dark and under 360 – 400 nm
broadband irradiation. Table summarizes results of the
1
photochemical reaction between 1 and the azides. The photo-
triggering nature of the reaction was evidenced by the lack of
reactivity in the absence of irradiation or the phosphonium cation
1. On the other hand, the photo-triggered reaction between 1
and the azides produced numerous identifiable products.
Without pH buffering, the corresponding amines of the three
azides were the major products. This is probably caused by the
significant drop in pH of the aqueous organic media upon
photolysis of 1, due to the formation of the anthracenylmethyl
Figure 1. Molecular structure of 1.
Spectral efficiency of the photo-induced conversion of 1 to
2
was assessed by monitoring the relative amount of 2 formed
after irradiation with a various absorption maxima of 1 (341, 375,
31
3
66, 376 and 396 nm) in d
8
-THF/D
2
O by P NMR (Fig. 4). The
carbocation
via
the
heterolytic
cleavage
of
the
highest relative yield of 2 was obtained with ex = 376 nm.
Attempt to quantify the quantum efficiency of the photo-induced
anthracenylmethyl-phosphine bond. Subsequent nucleophilic
attack of the carbocation by water leads to lowering of media pH.

Chemistry - A European Journal
10.1002/chem.201601807
COMMUNICATION
1
9
Tam et al. pointed out that at low media pH, protonation of the
iminophosphorane-N generated by the Staudinger-Bertozzi
ligation reaction would hinder the intramolecular nucleophilic
attack on the intramolecular electrophilic trap and render the
adjacent iminophosphorane-P more electrophilic. The attack of
water on that phosphorus would ultimately lead to the formation
of amines and phosphine oxide. To avoid this undesirable
reaction to occur, media pH for the present photo-triggered
traceless Staudinger-Bertozzi reaction was buffered to pH 7.4.
High buffer pH was not attempted because of the anticipated
instability of the thioester moiety of 1 towards hydrolysis. At this
physiological relevant media pH, the overall yield of the photo-
triggered traceless Staudinger-Bertozzi ligation reaction was 45
photolysis of the azide in the one-pot reaction, even if it occurred,
has not affected the overall yield of the photo-triggered
Staudinger-Bertozzi ligation reaction. The overall mechanism for
the photo-triggered traceless Staudinger-Bertozzi ligation
reaction is given in Fig. S10 in the Supporting Information.
In summary, we have demonstrated that photo-triggered
Staudinger-Bertozzi ligation can be effected by the photolysis of
phosphonium salts. This was verified by a specially designed
photo-triggered traceless Staudinger-Bertozzi ligation reagent, 1,
conveniently formed from 9-(chloromethyl)anthracene and the
diphenylphosphinothioester 2. Photolysis at 360 – 400 nm
induces the heterolytic cleavage of the anthracenylmethyl-
–
55 % (based on 1) for the three azides. In light of the
phosphorus
bond
in
1
and
releases
the
competing intramolecular aza-wittig reaction of the
diphenylphosphinothioester 2 for traceless Staudinger-Bertozzi
ligation reaction in aqueous organic media buffered at
physiological relevant pH. The quantum yield of such photo-
induced release of 2 is found to be  7 % at room temperature at
optimal wavelength (376 nm). The overall yield of the traceless
Staudinger-Bertozzi ligation process can be 45 – 55 %. The
most attractive feature of this photo-triggered traceless
Staudinger-Bertozzi ligation is that it does not leave behind any
residual functional group or chemical moiety after conjugation
that might interfere with the functioning, especially in terms of
biochemical and metabolic properties, of the conjugation
products. Thus, the present approach in the photo-regulation of
the Staudinger-Bertozzi ligation process may become a useful
tool for bio-conjugation and surface modification of materials.
1
8
iminophosphoranes , the ligation yields are considered
acceptable. Photolysis of the azides under the experimental
conditions was not observed.
31
P NMR
Photo irradiated for 10 min (ex = 360 – 400 nm)
Authentic standard
2
31
1
1
P NMR
H NMR





ex = 396 nm
ex = 376 nm
Photo irradiated for 10 min (ex = 360 – 400 nm)
ex = 366 nm
ex = 357 nm
ex = 341 nm
Authentic standard
3
1
1
Figure 3. P-
&
H
NMR evidences of photo-induced release of the
-THF/D O. Broadband
diphenylphosphinothioester 2 from 1 in degassed 3:1 d
8
2
photo-excitation (ex = 360 – 400 nm) was administered by a 500 W Hg lamp.
31
Figure 4. P NMR of degassed 3:1 d
8 2
-THF/D O solutions of 1 (25 mM) after
To ascertain whether the occurrence of any side-reaction
caused by the photolysis of the aliphatic azides has also
contributed to the reduction in product yield, we have also
attempted a two-stage approach to the photo-triggered ligation.
The buffered aqueous THF solution of 1 was photolyzed first in
the absence of azide 8. Then the azide substrate was added to
the photolyzed mixture and photo-irradiation was discontinued to
allow the subsequent reaction to proceed in dark. A yield of 50%
of the resultant conjugation product was eventually obtained.
This compares well with the one-pot photo-triggered Staudinger-
Bertozzi ligation reaction with azide 8, and suggest that
3
.5 h of irradiation at various excitation wavelengths. The minor singlet at
30.5 ppm is attributable to the phosphine-oxide of 2.
Experimental Section
All reagents were purchased and used without further purification unless
specified otherwise. Solvents for photolysis studies were degassed with
nitrogen. The diphenylphosphinothioester 2 was prepared according to
literature methods. Azide 8 – 10 were prepared according to the
literature-reported procedures.
spectra were recorded on
20
16,18,21
1
13
31
H
NMR,
C
NMR,
P NMR
a
400 MHz Bruker nuclear resonance

Chemistry - A European Journal
10.1002/chem.201601807
COMMUNICATION
31
spectrometer. P NMR spectra were proton-decoupled. High-resolution
mass spectrometry (electrospray ionization) analysis was performed by
the Analytical Instrumentation Center at Peking University, Shenzhen
Graduate School. Light source used for photolysis studies was a Newport
determination. Incident light intensities were taken from the average
values measured just before and after each photolysis experiment using
ferrioxalate actinometry. In the determination of the photochemical
quantum yield, a certain concentration solution of phosphonium salt 1 in
67005 500W Hg lamp equipped with a Newport 61945 IR reducer.
2
3:1 THF/H O was prepared. The quantum yield was determined at a
Broadband irradiation was achieved using optical filters of appropriate
cut-off wavelengths (Newport & Edmund). Quantum yield measurements
at specific excitation wavelength were carried out using a Newport 77200
monochromator. Qualitative and quantitative determination of reaction
products were carried out using an Agilent 7890 gas-chromatography
equipped with a Agilent 5975C mass spectrometer.
small percentage of conversion by monitoring the moles of the
diphenylphosphinothioester 2 generated by GC-MS (Agilent 7890/5975C).
Analytical photolyses were performed by irradiation of sample solution in
a 1cm quartz cell, using 500W Hg Lamp (Newport 67005) equipped with
a monochromator (Newport 77200) to give 366 nm UV light.
General procedure for the phototriggered traceless Staudinger-
Bertozzi ligation. Preparative photolyses were conducted by irradiation
a solution of 0.4 mmol phosphonium salt 1 and 0.4 mmol of azide in a 4
Preparation of 9-anthracenylmethyl diphenylphosphonium salt (1).
Diphenylphosphinothioester (2) (2.61 g, 9.5 mmol) and 9-
(
chloromethyl)anthracene (2.60 g, 11.5 mmol) were dissolved in
chloroform (2 mL). The resulting solution was stirred at ambient
temperature under N for 12 hours. The reaction mixture was added to
00 mL diethyl ether, stirred for 2 hours and filtered to give the
2 4 2 4
ml 3:1 THF/buffer (0.5 M K HPO / KH PO , pH 7.4) using a 500W Hg
Lamp (Newport 67005) equipped with an IR reducer (Newport 61945)
and convex lens. One long wave pass filter (360 nm, Newport) and a
short wave pass filter (400nm, Edmund) were used to give a band UV
light (360-400 nm). In a typical run, the mixture of azide substrate and
phosphonium salt 1 was photolyzed for 90 min. and was allowed to stand
for another 16 hours. The consumption of starting material was
2
2
1
phosphonium salt (1) as a light yellow solid (4.3 g, 91%). H NMR (400
MHz, CDCl ) δ 8.32 (d, J = 3.7 Hz, 1H), 8.15–8.24 (m, 2H), 7.82–7.90 (m,
H), 7.44–7.55 (m, 6H), 7.26–7.37 (m, 8H), 6.05 (d, J = 15.1 Hz, 2H),
3
2
5
13
31
.10 (d, J = 8.5 Hz, 2H), 2.11 (s, 3H) ppm. C NMR (400 MHz, CDCl
3
): δ
monitored with P NMR. After that, the solvent was removed in vacuo,
1
1
1
1
90.90 (d, J = 8.0 Hz), 134.78 (d, J = 12.0 Hz), 133.88 (d, J = 36.0 Hz),
30.94 (d, J = 20.0 Hz), 130.87 (d, J = 24.0 Hz), 129.30 (d, J = 48.0 Hz),
28.98 (d, J = 4.0 Hz), 128.81(d, J = 24.0 Hz), 126.85 (d, J = 8.0 Hz),
25.11 (d, J = 4.0 Hz), 124.32 (d, J = 12.0 Hz), 118.79 (d, J = 44.0 Hz),
15.70 (d, J = 332.0 Hz), 29.78, 25.51 (d, J = 176.0 Hz), 20.94 (d, J =
the residue was purified by flash chromatography on silica gel to isolate
the final amide product.
1
31
Acknowledgements
196.0 Hz) ppm. P NMR (400 MHz, CDCl
3
): δ 27.48 ppm. HRMS (ESI)
-
+
m/z calcd for C30
H26OPS [M-Cl ] 465.1442, found 465.1448, fragment at
1
91.0874.
This work is support by a grant from Research Grants Council of
the Hong Kong Special Administrative Region, China [Reference
No. CityU 11301414].
General procedure for the photolysis studies and quantum yield
measurement. Photolysis studies were performed by irradiation of
degassed solutions of 1 in deuterated solvents in NMR tubes. Chemical
actinometry was employed for the photochemical quantum yield
Keywords: Photo-triggering • Staudinger-Bertozzi ligation •
Conjugation reaction • Photolysis • Phosphonium salt
2
Table 1. Photo-triggered traceless Staudinger-Bertozzi ligation reactions with selected aliphatic azides in 3:1 THF/H O.
RN
3
R =
3
60 – 400 nm
photolysis
Staudinger-Bertozzi
conjugation product
Staudingder-
azide
photolysis
media pH
traceless Staudingder-Bertozzi
remark
Bertozzi reagent
ligation product yield (%)
-
-
-
1
1
1
1
1
1
-
-
-
8
9
10
8
9
10
8
9
10
8
9
10
360 – 400 nm
360 – 400 nm
360 – 400 nm
--
7.4
7.4
7.4
7.4
7.4
N.D.
N.D.
N.D.
N.D.
N.D.
N.D.
N.D.
N.D.
N.D.
52
--
--
7.4
360 – 400 nm
360 – 400 nm
360 – 400 nm
360 – 400 nm
360 – 400 nm
360 – 400 nm
unbuffered
unbuffered
unbuffered
7.4
major product: amine of 8
major product: amine of 9
major product: amine of 10
1
1
1
7.4
7.4
55
45
N.D. = not detected

Chemistry - A European Journal
10.1002/chem.201601807
COMMUNICATION
1.
.
H. Staudinger, J. Meyer, Helv. Chim. Acta, 1919, 2, 635.
20.
21.
a) N. J. Lawrence, J. Liddle, D. Jackson, J. Chem. Soc., Perkin Trans.,
2002, 1, 2260; b) M. B. Soellner, A. Tam, R. T. Raines, J. Org. Chem.,
2006, 71, 9824.
2
a) Y. G. Gololobov, L. F. Kasukhin, Tetrahedron, 1992, 48, 1353; b) P.
M. Fresnada, P. Molina, Synlett., 2004, 1; c) M. Köhn, R. Breinbauer,
Angew Chem. Int. Ed., 2004, 43, 3106.
C. J. Huang, F. –C. Chang, Macromolecules, 2009, 42, 5155.
3.
a) E. Saxon, C. R. Bertozzi, Science, 2000, 287, 2007; b) E. Saxon, J. I.
Armstrong, C. R. Bertozzi, Org. Lett., 2000, 2, 2141; c) E. Saxon, S. J.
Luchansky, H. C. Hang, C. Yu, S. C. Lee, C. R. Bertozzi, J. Am. Chem.
Soc., 2002, 124, 14893; d) G. A. Lemieux, C. L. de Graffenried, C. R.
Bertozzi, J. Am. Chem. Soc., 2003, 125, 4708; e) M. J. Hangauer, C. R.
Bertozzi, Angew. Chem. Int. Ed., 2008, 47, 2394.
4.
a) R. A. Chandra, E. D. Douglas, R. A. Mathies, C. R. Bertozzi, M. B.
Francis, Angew. Chem. Int. Ed., 2006, 45, 896; b) A. Watzke, M.
Gutierrez-Rodriguez, R. Wacker, H. Schröder, R. Breinbauer, J.
Kuhlmann, K. Alexandrov, C. M. Niemeyer, R. S. Goody, H. Waldmann,
Angew. Chem. Int. Ed., 2006, 45, 1408; c) R. Kleineweischede, C. P. R.
Hackenberger, Angew. Chem. Int. Ed., 2008, 47, 5984; d) Z. Pianowski,
K. Gorska, L. Oswald, C. A. Merten, N. Winssinger, J. Am. Chem. Soc.,
2009, 131, 6492; e) Y. Y. A. Lin, O. Boutureira, L. Lercher, B. Bhushan,
R. S. Paton, B. G. Davis, J. Am. Chem. Soc., 2013, 135, 12156.
nd
5
.
.
a) R. C. Jaeger, Introduction to Microelectronic Fabrication, 2 Ed.,
Prentice Hall, Upper Saddle River, 2002; b) A. Pimpin, W. Srituravanich,
Engineer. J., 2011, 16, 38.
6
a) J. A. McCray, L. Herbette, T. Kihara, D. R. Trentham, PNAS, 1980,
77, 7237; b) N. Wu, A. Deiters, T. A. Cropp, D. King, P. G. Schultz, J.
Am. Chem. Soc., 2004, 126, 14306; c) M. S. Kim, S. L. Diamond,
Bioorg. Med. Chem. Lett., 2006, 16, 5572; d) P. Rathert, T. Raskó, M.
Roth, K. Slaska-Kiss, A. Pingoud, A. Kiss, A. Jeltsch, ChemBioChem,
2007, 8, 202; e) E. A. Lemke, D. Summerer, B. H. Geierstanger, S. M.
Brittain, P. G. Schultz, Nat. Chem. Biol., 2007, 3, 769; f) T. Kurpiers, H.
D. Mootz, Angew. Chem. Int. Ed., 2009, 48, 2; g) D. Maurel, S. Banala,
T. Laroche, K. Johnsson, ACS Chem. Biol., 2010, 5, 507; h) J. Hemphill,
C. Chou, J. W. Chin, A. Deiters, J. Am. Chem. Soc., 2013, 135, 13433.
a) B. J. Adzima, Y. Tao, C. J. Klozin, C. A. DeForest, K. S. Anseth, C. N.
Bowman, Nat. Chem., 2011, 3, 256; b) R. T. Chen, S. Marchesan, R. A.
Evans, K. E. Styan, G. K. Such, A. Postma, K. M. McLean, B. W. Muir,
F. Caruso, Biomacromolecules, 2012, 13, 889; c) M. A. Tasdelen, Y.
Yagci, Angew. Chem Int. Ed., 2013, 52, 5930, and references therein.
C. E. Hoyle, A. B. Lowe, C. N. Bowman, Chem. Soc. Rev., 2010, 39,
7
8
.
.
1
355.
a) Y. Z. Wang, W. J. Song, W. J. Hu, Q. Lin, Angew Chem. Int. Ed.,
009, 48, 5330; b) Z. Yu, T. Y. Ohulchanskyy, P. An, P. N. Prasad, Q.
9
2
Lin, J. Am. Chem. Soc., 2013, 135, 16766; c) C. P. Ramil, Q. Lin, Curr.
Opin. Chem. Biol., 2014, 89.
1
0. a) T. Pauloehrl, G. Delaittre, V. Winkler, A. Welle, M. Bruns, H. Böerner,
A. M. Greiner, D. M. Bastmeyer, C. Barner-Kowollik, Angew. Chem. Int.
Ed., 2012, 51, 1071; b) T. Junkers, Eur. Polym. J., 2015, 62, 273.
11.
A. A. Poloukhtine, N. E. Mbua, M. A. Wolfert, G. –J. Boons, V. V. Popik,
J. Am. Chem. Soc., 2009, 131, 15769.
12.
T. Pauloehrl, G. Delaittre, V. Winkler, A. Wells, M. Bruns, H. G. Börner,
A. M. Greiner, M. Bastmeyer, C. Barner-Kowollik, Angew. Chem. Int.
Ed., 2012, 51, 1071.
1
3.
4.
a) R. R. da Silva, V. G. Toscano, R. G. Weiss, J. Chem. Soc., Chem.
Commun., 1973, 567; b) R. R. da Silva, F. H. Quina, V. G. Toscano, R.
G. Weiss, J. Phys. Chem., 1979, 83, 1213; c) T. M. S. Peranovich, M. E.
R. Marcondes, V. G. Toscano, Phosphorus, Sulfur, and Silicon and
Related Elements, 1990, 51, 314.
1
a) E. O. Alonso, L. J. Johnston, J. C. Scaiano, V. G. Toscano, J. Am.
Chem. Soc., 1990, 112, 1270; b) J. Ammer, C. F. Sailer, E. Riedle, H.
Mayr, J. Am. Chem. Soc., 2012, 134, 11481.
1
1
1
5. a) B. L. Nilsson, L. L. Kiessling, R. T. Raines, Org. Lett., 2000, 2, 1939; b)
B. L. Nilsson, L. L. Klessling, R. T. Raines, Org. Lett., 2001, 3, 9.
6.(a) B. Kempf, H. Mayr, Chem. Eur. J., 2005, 11, 917; b) K. Troshan, C.
Schindele, H. Mayr, J. Org. Chem., 2011, 76, 9391.
7.
a) C. G. Hatchard, C. A. Parker, Proc. R. Soc. London, Ser. A., 1956,
35, 518; b) J. N. Demas, W. D. Bowman, E. F. Zalewski, R. A.
2
Velapoldi, J. Phys. Chem., 1981, 85, 2766.
1
8.
9.
M. B. Soellner, B. L. Nilsson, R. T. Raines, J. Am. Soc. Chem., 2006,
1
28, 8820.
A. Tam, M. B. Soellner, R. T. Raines, J. Am. Chem. Soc., 2007, 129,
1421.
1
1

Chemistry - A European Journal
10.1002/chem.201601807
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
A 9-anthracenylmethyl-
Peng Hu, Tianshi Feng, Chi-Chung
phosphinothioester is a photo-caged
traceless Staudinger-Bertozzi ligation
reagent.
Yeung, Chi-Kin Koo, Kai-Chung Lau,
Michael H. W. Lam*
Page No. – Page No.
A Photo-triggered Traceless
Staudinger-Bertozzi Ligation
Reaction